Polylactic acid (PLA) is a biodegradable polyester that may be derived from renewable resources such as corn, rice or other sugar- or starch-producing plants. PLA can be easily processed by extrusion, injection, molding, film formation, etc., allowing a large range of applications, particularly for short-term uses (i.e., food packaging, bags, films, etc.). Furthermore, because of the non-toxicity of lactic acid monomers, PLA is one of the most promising biopolymers for medical applications. Due to their excellent biocompatibility and mechanical properties, PLA and their copolymers are becoming widely used in tissue engineering for function restoration of impaired tissues, in drug delivery systems and in various medical implants.
Lactic acid polymers can be synthesized by different processes so as to obtain products with an ample variety of chemical and mechanical properties. More particularly, PLA is mainly synthesized by two methods: the polycondensation of lactic acid (LA), which is carried out in bulk or in solution; or the ring-opening polymerization of lactide (cyclic dimer of lactic acid), which requires catalysts. The direct polycondensation of lactic acid in bulk is not applied on a great scale, because of the competitive reaction of lactide formation and the simultaneously occurring degradation process. The polycondensation of lactic acid in solution gives PLA with molecular weights ranging from the tens to a few hundred thousand g/mol. So far, the synthesis of PLA from lactide is the most effective method of synthesis in industry. However, the use of metal catalysts, cationic catalysts and/or organic catalysts may impact the quality of final product, some catalyst residues being incorporated into the polymer. Moreover, the racemization of part of the lactides during the process may lead to heteropolymers comprising both L-lactic acid and D-lactic acid. In addition this chemical polymerization requires high energetic inputs (heat) that bring additional economic and environmental costs.
Recently, alternative biological processes have been developed, wherein prokaryote cells such as bacteria have been engineered for producing microbial LA-based polyesters. This biological production takes advantage of the enzymatic activity of a polyhydroxyalkanoate (PHA) synthase leading to the production of LA-based polyesters. More precisely, the pathway for utilizing lactyl-CoA as a substrate for the production of LA-based polyesters has been developed in bacteria. However, the main polymer produced by this biological process is a copolymer composed of LA and other PHA (hydroxyacids or hydroxyalkanoate such as 3-hydroxybutyrate) monomers. The resulting copolymers, such as P(3HB-co-LA) have limited mechanical and industrial interest. Furthermore, the PLA polymers generated by this method are amorphous and have a low molecular weight (less than 30,000 g/mol). Such PLA exhibits poor mechanical properties and may not be easily processed in industrial applications such as injection molding, thermoforming or extrusion. Accordingly, such polymer is of low industrial interest.
The present invention describes novel biological methods and microorganisms for producing PLA. The invention allows effective production of homopolymers of PLA with high molecular weight, on large scale.